Hybrid printing platform for 3d bioprinting of live organs

Abstract

A method of forming a three dimensional object includes dispensing droplets of an electromagnetic energy curable liquid onto a surface to form a plurality of layers of the three dimensional object in liquid form, wherein each droplet forms a layer of liquid on the surface which is larger than a minimum feature size of a structure to be formed by curing the curable liquid, and directing electromagnetic energy capable of curing the liquid and having a beam width intersecting the layer of liquid which is at least as small as the smallest feature of a structure to be formed in the curable liquid.

What is claimed is: 
     
         1 . A method of forming an artificial organoid having bioactive cells, comprising:
 dispensing droplets of an electromagnetic energy curable bioink onto a surface to form a plurality of layers of the organoid in liquid form, wherein the droplets of bioink contain bioactive cell types therein of a structure to be formed in the organoid, and each droplet form a layer of bioink on the surface which is larger than a minimum feature size of a structure to be formed by curing the curable bioink; and   directing electromagnetic energy capable of curing the bioink having the bioactive cells into the layer of bioink, the electromagnetic energy having a beam width intersecting the bioink which is at least as small as the smallest feature of a structure to be formed in the organoid.   
     
     
         2 . The method of  claim 1 , wherein the bioink is selectively cured using the electromagnetic energy. 
     
     
         3 . The method of  claim 2 , further comprising forming multiple layers, one over the other, to form an organoid after completely forming all of the layers; and
 selectively curing all of the layers.   
     
     
         4 . The method of  claim 2 , further comprising forming multiple layers, one over the other, to form an organoids; and
 incubating the organoid under appropriate cell growth conditions to mature or repair the organ.   
     
     
         5 . The method of  claim 1 , wherein a bioink droplet forms a bioink layer on the surface as small as 10 um. 
     
     
         6 . The method of  claim 5 , wherein the curing selectively solidifies the biomaterial to a size having a cured dimension less than 10 um in size. 
     
     
         7 . The method of  claim 1 , wherein the surface is a previously formed, and cured layer of bioink. 
     
     
         8 . An apparatus useful for forming an artificial organoid having bioactive cells, comprising:
 a liquid dispensing device capable of dispensing droplets of an electromagnetic energy curable bioink onto a surface to form a slice of the organoid in liquid form, wherein the droplets of bioink contain bioactive cell types therein of a structure to be formed in the organoid, and a droplet forms an area larger than the smallest feature of the structure to be formed in the organoid; and   an electromagnetic beam directing device configured to direct electromagnetic energy capable of curing the bioink with the bioactive cells, the electromagnetic energy having a beam area intersecting the bioink which is smaller in width than the smallest feature of a structure to be formed in the organoid.   
     
     
         9 . The apparatus of  claim 8 , further comprising a stage mounted on a moveable sub configured to selectively position the surface onto which the droplets are located below the liquid dispensing device. 
     
     
         10 . The apparatus of  claim 9 , wherein the moveable sub is further configured to move the sate under the electromagnetic beam directing device. 
     
     
         11 . The apparatus of  claim 10 , wherein the direction from the surface is positioned on, or in, a carrier, and the carrier is positioned on the stage. 
     
     
         12 . The apparatus of  claim 10 , further comprising a controller operatively coupled to the moveable sub, the electromagnetic beam directing device and the liquid dispensing device. 
     
     
         13 . The apparatus of  claim 8 , wherein the liquid dispensing device includes at least two nozzles selectively openable to release a curable liquid therefrom, wherein the plurality of nozzles include a first nozzle connected to a supply of a first liquid having a first cell type therein, and a second nozzle connected to a supply of a second liquid having a second cell type therein, and the first cell type and the second cell type are different. 
     
     
         14 . The apparatus of  claim 13 , wherein, a droplet of the first liquid forms a layer on the surface which is smaller than a feature to be cured therein, and the second liquid forms a layer on the surface which is larger than a feature to be cured therein. 
     
     
         15 . An apparatus for forming a three dimensional object by sequentially dispensing liquid, in droplet form, to form a first liquid layer on a surface, at least partially curing that first layer to form a first feature having a minimum dimension therein, sequentially dispensing liquid, in droplet form, to form a second layer on the first at least partially cured layer, and, at least partially curing that second layer to form a second feature having a minimum dimension therein, comprising:
 a liquid dispensing device including at least one selectively openable nozzle connected to a supply of a liquid material, the nozzle capable of dispensing therefrom a droplet of at least a minimum volume, that droplet, when in contact with one of the surface of the at least partially cured first layer, having a thickness and an area over the one of the one of the surface of the at least partially cured first layer which is greater than the minimum dimension; and   an electromagnetic beam directing device outputting a beam of electromagnetic energy capable of curing, into a solid form, at least a portion of the material of the droplet, the beam of electromagnetic energy having a width dimension equal to, or less than, the minimum dimension.   
     
     
         16 . The apparatus of  claim 15 , wherein the at least one selectively openable nozzle includes at least a first nozzle in fluid communication with a first liquid, and a second nozzle in fluid communication with a second nozzle, and at least one component of the first liquid is different from any component of the second liquid. 
     
     
         17 . The apparatus of  claim 16 , wherein the first and second liquids each contain living cells, and the living cells in the first liquid are different than the living cells in the second liquid. 
     
     
         18 . The apparatus of  claim 17 , wherein the at least one selectively openable nozzle includes a third nozzle connected to a supply of liquid having a component thereof different than the components of the first liquid and the second liquid. 
     
     
         19 . The apparatus of  claim 16 , further comprising a moveable stage configured to move the surface first under the liquid dispensing device and then under the electromagnetic beam directing device. 
     
     
         20 . The apparatus of  claim 19 , wherein the moveable stage is moveable in a first direction extending in the direction of from the liquid dispensing device to the electromagnetic beam directing device, and a second direction crossing the first direction.